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CD138 multiple myeloma

Irena Misiewicz-Krzeminska, Luis Antonio Corchete, Elizabeta A Rojas, Joaquín Martínez-López, Ramón García-Sanz, Albert Oriol, Joan Bladé, Juan José Lahuerta, Jesús San Miguel, María Victoria Mateos, Norma C Gutiérrez
Protein analysis in bone marrow samples from patients with multiple myeloma has been limited by the low protein concentration obtained after CD138+ selection. A novel approach based on capillary nano-immunoassay could make it possible to automatically quantify dozens of proteins from each myeloma sample. Here, we present a method for the accurate and robust quantification of the expression of multiple proteins extracted from CD138-purified multiple myeloma samples frozen in RLT Plus buffer, which is commonly used for nucleic acid preservation and isolation...
March 15, 2018: Haematologica
Clément Bailly, Sébastien Gouard, Marie Lacombe, Patricia Remaud-Le Saëc, Benjamin Chalopin, Mickaël Bourgeois, Nicolas Chouin, Raphaël Tripier, Zakaria Halime, Ferid Haddad, Alain Faivre-Chauvet, Françoise Kraeber-Bodéré, Michel Chérel, Caroline Bodet-Milin
Purpose: Although recent data from the literature suggest that PET imaging with [18]-Fluorodeoxyglucose (18 F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker in many laboratories for the identification and purification of myeloma cells, and could be used in phenotype tumor imaging. In this study, we evaluated a64 Cu-labeled anti-CD138 murine antibody (64 Cu-TE2A-9E7.4) and a metabolic tracer (64 CuCl2 ) for PET imaging in a MM syngeneic mouse model...
February 6, 2018: Oncotarget
Jooeun Bae, Teru Hideshima, Yu-Tzu Tai, Yan Song, Paul Richardson, Noopur Raje, Nikhil C Munshi, Kenneth C Anderson
Histone deacetylases (HDAC) are therapeutic targets in multiple cancers. ACY241, an HDAC6 selective inhibitor, has shown anti-multiple myeloma (MM) activity in combination with immunomodulatory drugs and proteasome inhibitors. Here we show ACY241 significantly reduces the frequency of CD138+ MM cells, CD4+ CD25+ FoxP3+ regulatory T cells, and HLA-DRLow/- CD11b+ CD33+ myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8+ T cells and of immune checkpoints in bone marrow cells from myeloma patients...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xiaole Zhang, Lei Gao, Kai Meng, Chunting Han, Qiang Li, Zhenjun Feng, Lei Chen
Multiple myeloma (MM) is an incurable cancer characterized by the development of malignant plasma cells. The CD8 T cell-mediated cytotoxicity is considered a major player in antitumor immunity, but in MM patients, the CD8 T cells displayed senescence markers and were functionally impaired. To investigate whether cytotoxic CD4 T cells could act as a treatment alternative in MM, we examined the frequency and function of naturally occurring cytotoxic CD4 T cells in MM patients. The cytotoxic CD4 T cells were identified as granzyme-A, granzyme B-, and perforin-expressing CD4 T cells, and their frequencies were significantly upregulated in MM patients when compared with healthy controls...
February 12, 2018: Cellular Immunology
Atif Sohail, Adeela Mushtaq, Ahmad Iftikhar, Zabih Warraich, Sandra E Kurtin, Pavan Tenneti, Ali McBride, Faiz Anwer
We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...
February 1, 2018: Immunotherapy
Robert W Morris, Varsha Kumar, Ali G Saad
Solitary plasmacytoma is the rarest type of plasma cell neoplasm, and the anaplastic form is even more uncommon. Plasmacytoma most commonly originates in bone and predominantly affects older patients. We describe the case of a 35-year-old woman with solitary osseous anaplastic plasmacytoma that presented initially with a pathological fracture following minor trauma. The patient was immunocompetent and had no predisposing conditions for a plasma cell tumor. Left lower extremity radiographs revealed an oblique fracture of the distal femur, and CT imaging indicated a primary osseous lesion at the fracture site...
January 31, 2018: Skeletal Radiology
Joyce W Kamande, Maria A M Lindell, Małgorzata A Witek, Peter M Voorhees, Steven A Soper
Blood samples from patients with plasma cell disorders were analysed for the presence of circulating plasma cells (CPCs) using a microfluidic device modified with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs was higher in patients with symptomatic MM compared with MGUS and smouldering MM (p < 0...
January 26, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Andrew C Tiu, Vivian Arguello-Guerra, Gabor Varadi
Introduction: Multiple myeloma is caused by abnormal proliferation of plasma cells that affects more commonly African Americans. It classically presents with hypercalcemia, renal failure, anemia, and lytic bone lesions. The aim of this article is to present an unusual case of a 63-year-old African-American female with multiple myeloma who presented with worsening right-sided eye swelling for the past 3 weeks and to briefly review ophthalmologic manifestations of multiple myeloma. Case description: Our patient's presentation was associated with a throbbing frontal headache, nasal congestion, malaise, and weight loss...
2018: SAGE Open Medical Case Reports
Jiro Kikuchi, Yoshiaki Kuroda, Daisuke Koyama, Naoki Osada, Tohru Izumi, Hiroshi Yasui, Takakazu Kawase, Tatsuo Ichinohe, Yusuke Furukawa
Multiple myeloma (MM) cells acquire dormancy and drug resistance via interaction with bone marrow stroma cells (BMSC) in a hypoxic microenvironment. Elucidating the mechanisms underlying the regrowth of dormant clones may contribute to further improvement of the prognosis of MM patients. In this study, we find that the CD180/MD-1 complex, a non-canonical LPS receptor, is expressed on MM cells but not on normal counterparts, and its abundance is markedly upregulated under adherent and hypoxic conditions. Bacterial LPS and anti-CD180 antibody, but not other TLR ligands, enhanced the growth of MM cells via activation of MAP kinases ERK and JNK in positive correlation with expression levels of CD180...
January 23, 2018: Cancer Research
Sung-Hoon Jung, Seo-Yeon Ahn, Hyun-Woo Choi, Myung-Geun Shin, Seung-Shin Lee, Deok-Hwan Yang, Jae-Sook Ahn, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Background: Signal transducer and activator of transcription 3 (STAT3) is not only a key signaling molecule in the regulation of growth but is also involved in malignant transformation. We investigated the prognostic significance of STAT3 expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly diagnosed multiple myeloma (MM). Methods: Tumor cell-specific phosphotyrosine-STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual immunohistochemical (IHC) staining for PY-STAT3 and CD138...
December 2017: Blood Research
Sishi Tang, Dan Ma, Bingqing Cheng, Qing Fang, Xinyi Kuang, Kunling Yu, Weili Wang, Bo Hu, Jishi Wang
Inhibition of histone deacetylase (HDAC) is a promising therapeutic strategy for various hematologic cancers. Panobinostat has been approved for treating patients with multiple myeloma (MM) by the FDA. Since the mechanism for the resistance of panobinostat to MM remains elusive, we aimed to clarify this mechanism and the synergism of panobinostat with lenalidomide. The mRNA and protein of transcription factor IRF4 were overexpressed in CD138+ mononuclear cells from MM patients compared with in those from healthy donors...
January 6, 2018: Experimental Cell Research
Yuanyuan Sun, Jing Pan, Ning Zhang, Wei Wei, Shanshan Yu, Limei Ai
Long non-coding RNAs (lncRNAs) are implicated in the complex network of cancer including Multiple myeloma (MM) and play important roles in tumor development. lncH19 was significantly up-regulated in multiple cancer types, suggesting it is a potential oncogene. However, the exact functions and downstream mechanisms are largely unknown. This study aimed to investigate whether H19 participates in the cell growth of MM and elucidate the underlying mechanism. We found that H19 was abnormally overexpressed in MM cell lines and sorted CD138+ MM bone marrow tissues...
December 22, 2017: Scientific Reports
Diego M Carrion, Mario Álvarez-Maestro, Juan Gómez Rivas, Pilar González-Peramato, Jesús Cisneros Ledo
OBJECTIVE: We present the case of a patient diagnosed with a testicular extramedullary plasmacytoma (EMP), and perform a brief review of the literature of this pathology. METHODS: A 64 year-old male patient, with history of multiple myeloma successfully treated three years before, presented with left testicular swelling. Initial work-up was compatible with a testicular tumor and radical inguinal orchiectomy was performed. RESULTS: Histologic examination of the testis revealed extensive intertubular infiltration by CD138 and CD56 atypical plasma cells, with diffuse staining for IgA, compatible with EMP...
December 2017: Archivos Españoles de Urología
Suchada Sommaluan, Budsaba Rerkamnuaychoke, Teeraya Pauwilai, Suporn Chancharunee, Preeyaporn Onsod, Pitichai Pornsarayuth, Takol Chareonsirisuthigul, Rachaneekorn Tammachote, Teerapong Siriboonpiputtana
Multiple myeloma (MM) is a hematological malignancy characterized by abnormal accumulation of clonal plasma cells in the bone marrow. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for detection of common genetic alterations in MM patients. Here, we aimed to confirm MLPA utility for this purpose and furthermore to test the feasibility of a combination of karyotyping, interphase fluorescence in situ hybridization (iFISH) and MLPA methods for diagnosis, prognostic assessment and risk stratification of MM...
November 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
Hiroaki Kitamura, Yasushi Kubota, Kyosuke Yamaguchi, Kazuharu Kamachi, Atsujiro Nishioka, Masako Yokoo, Takero Shindo, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Solitary plasmacytoma of bone (SBP) tends to progress to multiple myeloma (MM); however, progression to multiple solitary plasmacytomas (MSP) is rare. We report a case of CD138-low MSP with 17p deletion in a patient with relapsed SBP. 17p deletion is associated with a poor outcome in patients with MM, and the low expression of CD138 in myeloma cells is associated with drug resistance and a poor prognosis. The patient was successfully treated with bortezomib plus dexamethasone induction therapy and autologous hematopoietic stem cell transplantation followed by bortezomib maintenance therapy...
November 20, 2017: Internal Medicine
Jing Liu, Yaming Wang, Yuantao Liu, Zhe Liu, Qu Cui, Nan Ji, Shengjun Sun, Bingxu Wang, Yajie Wang, Xuefei Sun, Yuanbo Liu
The majority of primary central nervous system lymphomas (PCNSLs) are diffuse large B cell lymphoma, characterized by poor prognosis. In the present study, the expression of cluster of differentiation (CD)10, B cell lymphoma (BCL)-6, multiple myeloma-1 (MUM-1), BCL-2, CD138 and Ki-67 was analyzed by immunohistochemistry in 89 Chinese PCNSL cases, and the potential prognostic significance was evaluated. CD10, BCL-6, MUM-1, BCL-2 and CD138 were positive in 16.9 (15/89), 51.7 (46/89), 92.1 (82/89), 73.3 (63/86) and 0% (0/65) of all cases, respectively...
November 2017: Oncology Letters
Katja Klausz, Michael Cieker, Christian Kellner, Hans-Heinrich Oberg, Dieter Kabelitz, Thomas Valerius, Renate Burger, Martin Gramatzki, Matthias Peipp
To identify antibodies suitable for multiple myeloma (MM) immunotherapy, a cellular screening approach was developed using plasma cell lines JK-6L and INA-6 and human synthetic single-chain fragment variable (scFv) phage libraries. Isolated phage antibodies were screened for myeloma cell surface reactivity. Due to its binding characteristics, phage PIII-15 was selected to generate the scFv-Fc fusion protein TP15-Fc with an Fc domain optimized for FcγRIIIa binding. Various MM cell lines and patient-derived CD138-positive malignant plasma cells, but not granulocytes, B or T lymphocytes from healthy donors were recognized by TP15-Fc...
September 29, 2017: Oncotarget
P Arana, B Paiva, M-T Cedena, N Puig, L Cordon, M-B Vidriales, N C Gutierrez, F Chiodi, L Burgos, L-L Anglada, J Martinez-Lopez, M-T Hernandez, A-I Teruel, M Gironella, M-A Echeveste, L Rosiñol, R Martinez, A Oriol, J De la Rubia, A Orfao, J Blade, J-J Lahuerta, M-V Mateos, J-F San Miguel
Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols...
November 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
XBP1 (X-box binding protein 1), CD138 (Syndecan-1), and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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